Asthma is a common disease that causes recurrent symptoms, repeated hospitalizations and an increased risk of sudden death. It is the most common childhood illness and affects 20 million Americans. According to the American Academy of Allergy, Asthma & Immunology, asthma causes direct health care costs in the United States of over $11.5 billion annually. Additionally, in the United States lost productivity adds another $4.6 billion and drugs prescribed for asthma patients represent costs of over $5 billion annually.
Asthma is characterized by acute bronchial constriction, chronic lung inflammation and airway hyperreactivity which results in chronic inflammation and airway remodeling that leads to progressive and possibly irreversible airway damage. The most effective therapy focuses on the early stages of the disease before the vicious cycle of inflammatory changes can become irreparable. The disease usually starts in early childhood and most commonly before five years of age. Thus, appropriate management of asthma in childhood may have a greater impact on the course of the disease than interventions later in life.
The mainstay of asthma treatment therapy is the use of anti-inflammatory drugs (i.e., inhaled corticosteroids). As a first line therapy for patients above five years of age, inhaled corticosteroids are usually given via an inhaler twice a day. Patients under five years of age are frequently given a nebulized form of budesonide (BUD), which is a potent inhaled corticosteroid, given twice a day as a first line therapy.
Although inhaled corticosteroids are very effective in preventing the massive inflammation that occurs with asthma, they do have some major drawbacks. One is that these drugs must be given at least daily to be effective. For instance, the effective life of BUD alone in the lungs is no more than one day. This daily dosage requirement may lead to non-adherence by the patient. Since adherence to daily use of inhaled corticosteriods by the patient is critical in interrupting the chronic inflammation that occurs in asthma, this becomes a focal issue for effective therapy. Further the effective use of an inhaler is very technique-dependent. Typically only up to about fifteen percent of a given dose is delivered to the lungs using an inhaler. The inhaled corticosteroids have a short half-life in the body and have potential toxicity when used in higher doses. These are serious disadvantages to the use of corticosteroid drugs in conventional therapy.
In an abstract published by the present inventors in the Journal of Allergy Clinical Immunology entitled “Efficacy of Liposome Encapsulated Budesonide in Experimental Asthma,” February, 2001, Vol. 107, No. 2, it is disclosed that BUD encapsulated in sterically stabilized liposomes prevents asthma inflammation in lower doses given at less frequent dosing intervals by comparison to daily BUD therapy. Test results are summarized demonstrating an improvement. The abstract does not disclose a suitable sterically stabilized liposome, suitable types of sterically stabilized liposomes or any method for producing a suitable sterically stabilized liposome, for producing BUD encapsulated in a suitable sterically stabilized liposome or a method for administering the sterically stabilized liposome containing BUD.
In view of the likelihood of possible adverse effects with use of corticosteroids and the frequency with which the corticosteroids and other drugs are required, a continued effort has been directed to the development of improved techniques for administering a drug to a mammal via the respiratory tract of the mammal so that it may be administered more effectively and so that the effectiveness of the drug can be achieved using smaller doses and at less frequent dosing intervals.